| Function: |
Signal transducer and transcription activator that mediates cellular responses to interferons (IFNs), cytokine KITLG/SCF and other cytokines and other growth factors. Following type I IFN (IFN-alpha and IFN-beta) binding to cell surface receptors, signaling via protein kinases leads to activation of Jak kinases (TYK2 and JAK1) and to tyrosine phosphorylation of STAT1 and STAT2. The phosphorylated STATs dimerize and associate with ISGF3G/IRF-9 to form a complex termed ISGF3 transcription factor, that enters the nucleus. ISGF3 binds to the IFN stimulated response element (ISRE) to activate the transcription of IFN-stimulated genes (ISG), which drive the cell in an antiviral state. In response to type II IFN (IFN-gamma), STAT1 is tyrosine- and serine-phosphorylated. It then forms a homodimer termed IFN-gamma-activated factor (GAF), migrates into the nucleus and binds to the IFN gamma activated sequence (GAS) to drive the expression of the target genes, inducing a cellular antiviral state. Becomes activated in response to KITLG/SCF and KIT signaling. May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4. |
| Involvement in Disease: |
Immunodeficiency 31B: A disorder characterized by susceptibility to severe mycobacterial and viral infections. Affected individuals can develop disseminated infections and die of viral illness.
Immunodeficiency 31A: A form of Mendelian susceptibility to mycobacterial disease, a rare condition caused by impairment of interferon-gamma mediated immunity. It is characterized by predisposition to illness caused by moderately virulent mycobacterial species, such as Bacillus Calmette-Guerin (BCG) vaccine, environmental non-tuberculous mycobacteria, and by the more virulent Mycobacterium tuberculosis. Other microorganisms rarely cause severe clinical disease in individuals with susceptibility to mycobacterial infections, with the exception of Salmonella which infects less than 50% of these individuals. Clinical outcome severity depends on the degree of impairment of interferon-gamma mediated immunity. Some patients die of overwhelming mycobacterial disease with lepromatous-like lesions in early childhood, whereas others develop, later in life, disseminated but curable infections with tuberculoid granulomas. IMD31A has low penetrance, and affected individuals have relatively mild disease and good prognosis. IMD31A confers a predisposition to mycobacterial infections only, with no increased susceptibility to viral infections.
Immunodeficiency 31C: A primary immunodeficiency disorder with altered immune responses and impaired clearance of fungal infections, selective against Candida. It is characterized by persistent and/or recurrent infections of the skin, nails and mucous membranes caused by organisms of the genus Candida, mainly Candida albicans. |
| Sequence Similarities: |
Belongs to the transcription factor STAT family. |
| Post-Translational Modification: |
Phosphorylated on tyrosine and serine residues in response to a variety of cytokines/growth hormones including IFN-alpha, IFN-gamma, PDGF and EGF. Activated KIT promotes phosphorylation on tyrosine residues and subsequent translocation to the nucleus. Upon EGF stimulation, phosphorylation on Tyr-701 (lacking in beta form) by JAK1, JAK2 or TYK2 promotes dimerization and subsequent translocation to the nucleus. Growth hormone (GH) activates STAT1 signaling only via JAK2. Tyrosine phosphorylated in response to constitutively activated FGFR1, FGFR2, FGFR3 and FGFR4. Phosphorylation on Ser-727 by several kinases including MAPK14, ERK1/2 and CAMKII on IFN-gamma stimulation, regulates STAT1 transcriptional activity. Phosphorylation on Ser-727 promotes sumoylation though increasing interaction with PIAS. Phosphorylation on Ser-727 by PRKCD induces apoptosis in response to DNA-damaging agents. Phosphorylated on tyrosine residues when PTK2/FAK1 is activated; most likely this is catalyzed by a SRC family kinase. Dephosphorylation on tyrosine residues by PTPN2 negatively regulates interferon-mediated signaling. Upon viral infection or IFN induction, phosphorylation on Ser-708 occurs much later than phosphorylation on Tyr-701 and is required for the binding of ISGF3 on the ISREs of a subset of IFN-stimulated genes IKBKE-dependent. Phosphorylation at Tyr-701 and Ser-708 are mutually exclusive, phosphorylation at Ser-708 requires previous dephosphorylation of Tyr-701. |
| Cellular Location: |
Cytoplasm. Nucleus.
Translocated into the nucleus upon tyrosine phosphorylation and dimerization, in response to IFN-gamma and signaling by activated FGFR1, FGFR2, FGFR3 or FGFR4. |
| Database Links: |
Entrez Gene: 6772?HumanEntrez Gene: 20846?MouseOmim: 600555?HumanSwissProt: P42224?HumanSwissProt: P42225?MouseUnigene: 642990?HumanUnigene: 743244?HumanUnigene: 277406?Mouse |
| Synonyms: |
Signal transducer and activator of transcription 1 91kD AntibodyCANDF7 AntibodyDKFZp686B04100 AntibodyIMD31A AntibodyIMD31B AntibodyIMD31C AntibodyISGF 3 AntibodyISGF-3 AntibodyOTTHUMP00000163552 AntibodyOTTHUMP00000165046 AntibodyOTTHUMP00000165047 AntibodyOTTHUMP00000205845 AntibodySignal transducer and activator of transcription 1 AntibodySignal transducer and activator of transcription 1 91kDa AntibodySignal transducer and activator of transcription 1, 91kD AntibodySignal transducer and activator of transcription 1-alpha/beta AntibodySTAT 1 AntibodySTAT1 AntibodySTAT1_HUMAN AntibodySTAT91 AntibodyTranscription factor ISGF 3 components p91 p84 AntibodyTranscription factor ISGF-3 components p91/p84 Antibody |
| Information: |
Target information shown above is from the UniProt Consortium. |
